Miniaturization of electronic devices necessitates the development of equally small power sources. For minimally invasive biomedical applications, these power sources should ideally be soft, biocompatible, biodegradable, and possess additional functionalities like triggerable activation and remote mobility. While hydrogel-based lithium-ion batteries offer some of these features, microscale fabrication integrating hydrogel-based cathode, separator, and anode at the submillimeter level has remained a challenge. Previous attempts using droplet-based devices have yielded miniature power sources, but a rechargeable version has been elusive. This research aims to address this gap by developing a microscale soft, rechargeable lithium-ion battery that meets the aforementioned criteria for biomedical applications. The authors highlight the limitations of previous droplet-based ionic power sources, such as low power output, limited rechargeability, complex activation, restricted functionality, and insufficient power for organ-level stimulation. This new LiDB aims to overcome these limitations, paving the way for a wider range of biomedical applications.

The miniaturization of electronic devices is a rapidly growing field of research, driving the need for smaller, more efficient batteries. Techniques like 3D printing and micro-origami assembly are being explored. For biomedicine, the demand for soft, biocompatible, and biodegradable batteries with features like triggerable activation and remote control is increasing. Hydrogel-based lithium-ion batteries show promise, but current limitations include difficulties in microscale fabrication due to the mixing of materials during the gelation process. Previous research has demonstrated miniaturized ionic power sources using lipid-supported networks of nanoliter hydrogel droplets, which mimic the electrical eel's mechanism, but suffer from low power output, non-rechargeability, complex activation, and limited functionality. This new LiDB addresses these limitations.

The LiDB consists of three silk hydrogel droplets: a cathode droplet (LiMn2O4 particles and carbon nanotubes), a separator droplet (LiCl), and an anode droplet (Li4Ti5O12 particles and carbon nanotubes). These droplets are deposited in lipid-containing oil using a microinjector. Lipid monolayers form droplet interface bilayers (DIBs) upon contact, preventing material diffusion and short circuits. The battery is activated by UV irradiation, which crosslinks the silk hydrogel and ruptures the DIBs, creating a continuous ion-conducting pathway. The silk hydrogel provides mechanical stability, high electrical conductivity, cation selectivity (due to negatively charged amino acids), biocompatibility, biodegradability, and strong tissue adhesion. The electrochemical characteristics of the LiDB are evaluated using cyclic voltammetry, galvanostatic charge-discharge measurements, and electrochemical impedance spectroscopy. Miniaturization is achieved by decreasing droplet volume, increasing the surface-to-volume ratio, and enhancing redox reactions. Multiple LiDB units can be connected in series to increase voltage. For charged molecule translocation, the LiDB is interfaced with synthetic cells (hydrogel droplets or aqueous droplets with αHL pores) using PEDOT:PSS converting droplets to transform electron current into ion flux. For *ex vivo* heart experiments, LiDBs are placed in direct contact with Langendorff-perfused murine hearts, and ECGs are recorded to monitor effects. Optogenetic light pacing is used to ensure accurate measurement of LiDB-induced heart activity. Magnetic maneuverability is achieved by incorporating magnetic nickel particles into the separator droplet, allowing controlled movement under a magnetic field. Biocompatibility is assessed through co-culture experiments with mouse fibroblasts, human dermal fibroblasts, and cardiomyocytes. Biodegradation is tested using proteinase K.

The LiDB demonstrated a high volumetric capacity (up to ~570 nAh µl⁻¹ for 10 nl droplets), exceeding previous all-hydrogel Li-ion batteries by more than 10³-fold. The device exhibited good cycle stability (over 72% capacity retention after 50 cycles at 1 µA). Serial connection of multiple units successfully powered LEDs and other electronic devices. The LiDB effectively powered tetherless electrophoretic translocation of charged molecules between synthetic cells within 10 minutes. In *ex vivo* mouse heart experiments, the LiDB successfully defibrillated hearts with ventricular arrhythmias (induced by ouabain) within 5 seconds and paced heart rhythms using a wired connection. The incorporation of magnetic particles enabled magnetically-controlled propulsion and steering of the LiDB, demonstrating its potential as a mobile energy courier. The LiDB functioned in both oil and aqueous (LiCl solution) environments, though capacity was reduced in the latter. Biocompatibility tests showed no adverse effects on cell viability and proliferation after 48 hours of co-culture with LiDBs. Enzymatic biodegradation of the silk hydrogel left only nanograms of residual materials.

The findings demonstrate the successful fabrication and characterization of a highly miniaturized, soft, rechargeable lithium-ion battery with biocompatible and biodegradable components. The LiDB's high energy density, on-demand activation, and ability to power charged molecule translocation and heart stimulation significantly advance the field of microscale energy storage. The magnetic maneuverability feature opens up possibilities for in vivo applications such as powering micro-robots. The successful application in *ex vivo* heart defibrillation and pacing showcases the potential for low-energy, minimally invasive cardiac treatments. This research addresses the limitations of previous miniature power sources and provides a promising platform for various biomedical applications.

This study successfully developed a microscale soft Li-ion battery (LiDB) with superior energy density and functionality. The LiDB's on-demand activation, biocompatibility, and magnetic maneuverability demonstrate potential for applications in microrobotics, synthetic tissues, and implantable medical devices. Future research could focus on increasing the mass loading of Li particles, exploring alternative droplet assembly techniques to enhance scalability and energy density, and testing the LiDB in in vivo settings.

The electrochemical stability window of water limits the output voltage of the LiDB, although serial connection can mitigate this. The mass loading of Li particles is currently limited to prevent nozzle clogging during fabrication, potentially reducing the maximum capacity. Further research is needed to optimize the fabrication process and explore alternative materials to address these limitations.